Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses

A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) fr...

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Main Authors: Pavesi, A, Magiorkinis, G, Karlin, D
Format: Journal article
Language:English
Published: Public Library of Science 2013
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author Pavesi, A
Magiorkinis, G
Karlin, D
author_facet Pavesi, A
Magiorkinis, G
Karlin, D
author_sort Pavesi, A
collection OXFORD
description A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such “gene nurseries” may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage.
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spelling oxford-uuid:7f1f5bb0-8c26-4969-9800-3e98b7978b132022-03-26T21:14:42ZViral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of DeltaretrovirusesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7f1f5bb0-8c26-4969-9800-3e98b7978b13EnglishSymplectic Elements at OxfordPublic Library of Science2013Pavesi, AMagiorkinis, GKarlin, DA well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such “gene nurseries” may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage.
spellingShingle Pavesi, A
Magiorkinis, G
Karlin, D
Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title_full Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title_fullStr Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title_full_unstemmed Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title_short Viral proteins originated de novo by overprinting can be identified by codon usage: application to the "gene nursery" of Deltaretroviruses
title_sort viral proteins originated de novo by overprinting can be identified by codon usage application to the gene nursery of deltaretroviruses
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AT karlind viralproteinsoriginateddenovobyoverprintingcanbeidentifiedbycodonusageapplicationtothegenenurseryofdeltaretroviruses